Psoriasis is a common inflammatory condition found in 1-2% of the population. Mild psoriasis is treated with primarily topical glucocorticoids, and other topical agents such as vitamin D and topical retinoids having a smaller role due to decreased efficacy. Severe psoriasis is often treated with systemic medications, including methotrexate, cyclosporine, and retinoids, and more recently with biological agents, such as soluble receptors to tumor necrosis factor α (TNFα), or antibodies to TNFα receptors. While these therapies are effective under some settings, all of them are associated with side effects. Hepatotoxicity is a major issue for long-term use of methotrexate and retinoids, while hypertension, nephropathy and systemic immunosuppression complicate the use of cyclosporine. Thus, there is a pressing need for effective topical therapies for psoriasis, especially those working through mechanisms that differ from those currently available.
The epidermal growth factor receptor (EGFR) is a cell membrane growth factor receptor. Aberrant signaling through the EGFR appears to be associated with angiogenesis. Normal angiogenesis plays an important role in a variety of processes including embryonic development, wound healing and several components of female reproductive function. However, undesirable or pathological angiogenesis has been associated with disease states including diabetic retinopathy, psoriasis, cancer, rheumatoid arthritis, atheroma, Kaposi's sarcoma and haemangioma (Fan et al (1995) Trends Pharmacol, 16: 57-66; Folkman (1995) Nat. Med. 1: 27-31). Development of effective preventive and treatment means has been hampered by inadequate understanding of the factors controlling this process.
Accordingly, a need exists for methods of treating a mammal having a disease or condition characterized by increased angiogenesis or aberrant EGFR signaling.